Premium
Protein Phosphatase 1 and 2A Inhibitors Prolong the Switch in the Control of Glutamate Release by Group I Metabotropic Glutamate Receptors
Author(s) -
Sistiaga Alessandra,
SánchezPrieto José
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751566.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 6 , glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 2 , protein kinase c , phosphatase , okadaic acid , metabotropic glutamate receptor 1 , chemistry , pertussis toxin , inhibitory postsynaptic potential , pharmacology , biochemistry , biology , receptor , endocrinology , g protein , signal transduction , phosphorylation
We have addressed the role of protein phosphatases (PPs) in the modulation of the switch in glutamate release observed after repetitive stimulation of group I metabotropic glutamate receptors (mGluRs). In cerebrocortical nerve terminals the agonist ( S )‐3,5‐dihydroxyphenylglycine facilitated evoked glutamate release. However, a second stimulation, 5 min later, reduced rather than facilitated this release. This switch in the control of glutamate release was reversed when a 30‐min interval was left between stimulations. Inhibition of the endogenous PPs, PP1 and PP2A, with calyculin A and okadaic acid prevented the recovery of the facilitatory response and maintained the receptor permanently coupled to the inhibitory pathway. The inhibitors of PP2B, cyclosporin A and cypermethrine, had no effect. The inhibition of glutamate release was insensitive to pertussis toxin and was the result of the loss of the release component coupled to N‐type Ca 2+ channels. This inhibitory action was suppressed by addition of the protein kinase C activator 4β‐phorbol 12,13‐dibutyrate. We conclude that the balance between protein kinase and phosphatase activity at the nerve terminal plays a key role in accommodating the modulation of glutamate release by group I mGluRs.